ALS is a motor neuron disease defined as a progressive, neurological disorder, resulting from variable and combined degeneration of upper and lower motor neurons. The heterogeneity of clinical involvement early in the course of the disease makes it difficult to diagnose, as well as to identify one unique outcome measure to quantify neurological changes in the course of the disease. Since clinical evidence of upper and lower motor neuron degeneration must exist in four anatomical regions (bulbar, cervical, thoracic, and lumbosacral), outcome measures should assess these regions. The WFN Airline House recommendations specify the purpose, properties, and the preferred parameters which serve as outcome measures in ALS clinical trials. The purpose of this document is to serve as a review of these outcome measures in terms of their advantages, disadvantages, sensitivity, reliability, and other characteristics, as well as their proper performance in ALS clinical trials. Generally these outcome measures are allocated to four areas: respiratory function, muscle strength, general function, and bulbar function. Our review leads us to believe that respiratory function and strength provide the most useful information, both for research and clinical purposes, and are essential as outcome measures. Inclusion of bulbar and general function parameters in trial design may increase the possibility of identifying a beneficial effect of therapeutic intervention. It is essential to note that the guidelines and recommendations put forth are intended to provide initial evaluation and critique of the proper employment and performance of these outcome measures in ALS clinical trials, based on the available literature and our experience.